Regions of the world that are endemic for tuberculosis (TB) are also endemic for helminthic infections. It is estimated that TB affects one-third of the world's population, with helminthic infections accounting for disease in over one quarter of the world's population. TB and helminthic infections pose a major public health concern, particularly in developing nations where the prevalence of both diseases is alarmingly high. Strategies aimed at combating parasitic infections may also help in control of the Big three killers: TB, HIV, and Malaria. Although it is known that protection to TB infection is dependant on development of a strong T helper (Th) 1 response, the effect of Th2 responses, elicited by helminths on the control of TB remains unclear. In this proposal we will use a mouse model of helminth/TB co-infection and real time PCR, immnohistochemistry, and flow cytometric techniques will be implemented to asses the effect of co-infection on bacterial burden, cytokine expression levels, and granuloma formation. The central goal of this proposal is to examine the mechanism for Th2 modulation of the protective immune response to TB infection and study its impact on the development of memory responses to re-infection in vivo. Overall we expect to obtain from these studies an insight into the factors that can modulate the Th1 protective immunity to TB. Successful completion of these studies will provide innovative strategies for vaccine development and also provide new modalities of modulating the immune response to shorten chemotherapy and/or overcome drug resistance. The specific aims that will address the goals of the proposal are: Aim 1 we will conduct in vivo infection studies to determine how helminth infections modulate the course of TB infection. Aim 2 of our study, we will determine the effect of co-infection in the development of effective memory T-cell responses to re-infection with TB.